Clinical significance of endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma.
- 作者列表："Cho HC","Kim JH","Cha RR","Kim WS","Lee JM","Lee SS","Kim HJ","Lee CM","Kim HJ","Ha CY","Kim TH","Jung WT","Lee OJ
BACKGROUND AND OBJECTIVE:The role of endothelial progenitor cells in patients with cirrhosis has seldom been investigated. This study was conducted to assess the clinical significance of circulating endothelial progenitor cells in patients with liver cirrhosis with or without hepatocellular carcinoma. METHODS:A blood sample was collected once from patients with cirrhosis alone (n = 34) or cirrhosis and hepatocellular carcinoma (n = 46) and healthy controls (n = 27) for assessing levels of endothelial progenitor cells and vascular endothelial growth factor. Blood cells staining positive for CD34/CD133/KDR using flow cytometry were characterized as endothelial progenitor cells. Plasma vascular endothelial growth factor was quantified by ELISA. RESULTS:The levels of CD34/KDR-positive endothelial progenitor cells, CD133/KDR-positive endothelial progenitor cells, and vascular endothelial growth factor were higher in patients with cirrhosis ± hepatocellular carcinoma than in healthy controls (P = 0.017, P < 0.001 and P < 0.001, respectively). The levels of endothelial progenitor cells and vascular endothelial growth factor did not show statistical difference according to Child-Turcotte-Pugh class. There was a moderately significant correlation between vascular endothelial growth factor levels and hepatocellular carcinoma stage (ρ = 0.464, P = 0.001). Smoking, ascites, and portal vein thrombosis were independently related to lower levels of circulating CD34/KDR-positive endothelial progenitor cells, higher levels of CD133/KDR-positive endothelial progenitor cells, and higher levels of vascular endothelial growth factor, respectively (P = 0.041, P = 0.023, and P < 0.001, respectively). CONCLUSION:Circulating endothelial progenitor cells and plasma vascular endothelial growth factor levels were higher in patients with liver cirrhosis ± hepatocellular carcinoma compared to healthy controls. The increase in endothelial progenitor cells and vascular endothelial growth factor may have a possible role in the development of complications, especially ascites and portal vein thrombosis, or in progression of hepatocellular carcinoma.
背景与目的：内皮祖细胞在肝硬化患者中的作用很少被研究。本研究旨在探讨肝硬化伴或不伴肝细胞癌患者循环内皮祖细胞的临床意义。 方法：单采肝硬化患者（34例）、肝硬化和肝癌患者（46例）和健康对照组（27例）各1次血，测定内皮祖细胞和血管内皮生长因子水平。流式细胞仪检测CD34/CD133/KDR阳性的血细胞为内皮祖细胞。ELISA法测定血浆血管内皮生长因子。 结果：肝硬化±肝癌组CD34/KDR阳性内皮祖细胞、CD133/KDR阳性内皮祖细胞和血管内皮生长因子水平均高于健康对照组（P分别为0.017、P<0.001和P<0.001）。根据Child-Turcotte-Pugh分级，内皮祖细胞和血管内皮生长因子水平无统计学差异。血管内皮生长因子水平与肝细胞癌分期有中度显著相关（P=0.464，P=0.001）。吸烟、腹水和门静脉血栓形成分别与低水平循环CD34/KDR阳性内皮祖细胞、高水平CD133/KDR阳性内皮祖细胞和高水平血管内皮生长因子有关（分别为P=0.041、P=0.023和P<0.001）。 结论：肝硬化±肝癌患者的循环内皮祖细胞和血浆血管内皮生长因子水平高于健康对照组。内皮祖细胞和血管内皮生长因子的增加可能在并发症的发生，特别是腹水和门静脉血栓形成，或肝细胞癌的进展中起作用。
METHODS:BACKGROUND:Opioids are often prescribed for pain in cirrhosis and may increase the risk of hepatic encephalopathy (HE). AIMS:To assess the association between opioids and HE in patients with well-compensated cirrhosis. METHODS:We used the IQVIA PharMetrics (Durham, NC) database to identify patients aged 18-64 years with cirrhosis. We excluded patients with any decompensation event from 1 year before cirrhosis diagnosis to 6 months after cirrhosis diagnosis. Over the 6 months after cirrhosis diagnosis, we determined the duration of continuous opioid use and classified use into short term (1-89 days) and chronic (90-180 days). We assessed whether patients developed HE over the subsequent year (ie 6-18 months after cirrhosis diagnosis). We used a landmark analysis and performed multivariable Cox proportional hazards regression to assess associations between opioid use and HE, adjusting for relevant confounders. RESULTS:The cohort included 6451 patients with compensated cirrhosis, of whom 23.3% and 4.7% had short-term and chronic opioid prescriptions respectively. Over the subsequent year, HE occurred in 6.3% patients with chronic opioid prescriptions, 5.0% with short-term opioid prescriptions and 3.3% with no opioid prescriptions. In the multivariable model, an increased risk of HE was observed with short-term (adjusted hazard ratio, HR 1.44, 95% CI 1.07-1.94) and chronic opioid prescriptions (adjusted HR 1.83, 95% CI 1.07-3.12) compared to no opioid prescriptions. CONCLUSION:In this national cohort of privately insured patients with cirrhosis, opioid prescriptions were associated with the risk of incident HE. Opioid use should be minimised in those with cirrhosis and, when required, limited to short duration.
METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.
METHODS:BACKGROUND:Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with liver cirrhosis. In recent years, it has been postulated that the rate of multidrug-resistant organisms (MDROs) is increasing, especially in nosocomial SBP patients. Aim of the present work was to investigate this hypothesis and its possible clinical consequences. MATERIALS AND METHODS:One hundred and three culture-positive patients between 2007 and 2014 were compared with 81 patients between 2015 and 2017, to study the change of microbiological profiles and their clinical consequences. The cirrhosis patients with bacterascites requiring treatment were included as well. RESULTS:The most prevalent Gram-negative bacteria isolated from ascites were Enterobacterales (31.6%) and in Gram-positive pathogens Staphylococci (22.8%). There was a significant increase in MDROs (22.3% ICU 40.7%, P = .048), accompanied by an increased incidence of sepsis (from 21.4% to 37.0%, P = .021), hepatorenal syndrome (from 40.8% to 58.0%, P = .007) and the need of catecholamine therapy (from 21.4% to 38.8%, P = .036). Nosocomial origin correlated with higher MDRO proportion, more complications and lower antimicrobial susceptibility rates in 12 commonly used antibiotics. MDROs were confirmed as an isolated predictor for inpatient mortality and complications in multivariable logistic regression. CONCLUSIONS:The feeling in clinical practice that MDROs have increased in the last 11 years could be confirmed in our study in Munich, Germany. Nosocomial SBP correlated with significantly higher MDRO rates (nearly 50%) and complication rates. In our opinion, an antibiotic combination with comprehensive effect should be taken into account in nosocomial SBP patients in this region.